Sadly it’s my final day in Paris, but the conference has finished in fine style with a selection of talks largely focusing on organometallic chemistry and catalysts. I have a soft spot for organometallic chemistry, and so too did the audience it seems, since the lecture theatre was full, even though many attendees were probably slightly hungover from last night’s conference dinner.

But then again, who would miss the chance to see Richard Schrock? He gave a fascinating talk describing the development of his (and Amir Hoveyda’s) stereogenic-at-metal catalysts for asymmetric metathesis reactions (Nature subscribers can read the first report of this work here; JACS subscribers can read the latest paper on the subject here). I was also interested to hear that he has developed catalysts that provide Z-products from metathesis reactions, which has led to the preparation of the first cis– syndiotactic polymer (described in another JACS paper). And there’s more to come – a paper reporting enantio- and endoselective enyne metathesis is currently in press.

So how do you follow that? With Steve Buchwald, of course. He dished out some great advice for those wanting to do C-N bond formations (and I know there are many of you). So, if you’re bewildered by the array of ligands for these reactions, he reckons that one of Xphos, RuPhos (named after his cat, Rufus, by the way) or BrettPhos (which is discussed in this JACS paper) will always do the job. He’s also come up with some useful precatalysts, which he reckons should overcome the problems some people have encountered when using this chemistry (see this JACS paper for a description of the precatalysts).

Not long now before I have to dash off to catch my train home, but there’s just time to mention Jose Barluenga’s talk that discussed the use of Fischer carbene complexes and late transition metal catalysis in organic synthesis (the latter including a rather nice modular approach for making indoles – Angewandte subscribers can read about this here). Perhaps most intriguing was his discussion of a metal-free coupling of tosylhydrazones with boronic acids to make diphenymethane compounds. These were preliminary results, so I’ll be intrigued to see the paper when it’s published.

Right, I’m off to the Gare du Nord. A bientot!

Andy

Andrew Mitchinson (Senior Editor, Nature)

Day two of my conference in sunny Paris, and the talks moved on this afternoon to biological chemistry. Long-term readers of this blog will know that I’m not a chemical biologist, so this will be a relatively brief overview of the topics discussed – but what topics!

Kim Janda largely focused on his work discovering antibodies for various therapeutic applications. I never knew that it might be possible to develop a vaccine for cocaine addiction, but Kim seems to be well on his way, with an antibody treatment that – in animal studies – reduces the amount of cocaine that passes through the blood-brain barrier, and which offers some protection against overdoses with the drug.

Carlos Barbas’s talk also strongly featured antibodies. I was particularly taken with his idea of using bifunctional antibodies in combination with prodrugs for anticancer therapy. The antibodies bind to tumours, but they also unmask anticancer agents from the prodrugs; this ensures that cytotoxic anticancer agents are targeted exclusively to tumours (which is good, because such agents are generally also toxic to healthy cells). He showed that a prodrug of the anticancer drug etoposide, when given to mice with appropriate antibodies, elicits a 75% reduction in tumour growth compared with controls, and with no signs of toxicity.

Thomas Carell gave a brilliant talk about his studies of DNA repair mechanisms, having isolated crystal structures of some of the enzymes concerned when in complex with damaged DNA. And here’s one of those mind-boggling statistics: apparently, in humans, every cell sustains 100,000 lesions to its DNA every day. So be thankful for your photolyases and Y-polymerases, which deal with the problem.

And finally, what was the dispute between George Whitesides and Jean-Marie Lehn yesterday? Well, George was discussing the problems of designing ligands for proteins – his conclusion is that our models for the hydrophobic effect and for how water molecules behave in proteins are basically wrong. But he also declared that the ‘lock-and-key’ model of enzyme-ligand interactions is bogus too: you don’t need a precise, tight fit, as implied by the model, but rather a ‘sloppy’ fit. Jean-Marie, however, defended the lock-and-key model, saying that, at the very least, it is the best way of explaining protein-ligand interactions for non-specialists. And then he went on to use the lock-and-key analogy in his slides.

More from Paris tomorrow…

Andy

Andrew Mitchinson (Senior Editor, Nature)

No, I don’t mean Ms Hilton. I’m at the Tenth Tetrahedron Symposium in Paris, celebrating 50 years of Tetrahedron Letters with a stunning programme of speakers – a real who’s who of organic chemists. If you ever have the chance to attend a conference in Paris, you’ve got to go, if only because it’s a foodie’s paradise. The three-course lunch was sensational, and the mini-desserts they’ve been dishing out during coffee breaks are to die for.

But I digress. Let me tell you about the chemistry. Catalysis was the unofficial theme of the morning’s talks. A highlight for me was Masakatsu Shibasaki’s discussion of his work developing asymmetric ‘two-centre’ catalysts (so-called because they contain two different metal atoms). I love hearing how original ideas extend into different directions, and this was a great example of that, as Masakatsu described how the discovery of catalysts for asymmetric Michael reactions led on to the development of catalysts for cyclopropanations, then for epoxide-formations and ultimately for making 2,2-disubstituted oxetanes (Angewandte Chemie subscribers can see the oxetane work here).

After lunch, a smorgasbord of treats awaited us (and not just the petits fours). Peter Vollhardt described unpublished work on the chemistry of phenylenes, including a fascinating description of haptotropism in their cobalt complexes. Michael Krische gave an overview of his work developing carbon-carbon bond-forming reactions via hydrogenations – appropriately enough for the venue, this work was inspired by seminal work from the French chemists Victor Grignard and Paul Sabatier. To my mind, this is a brilliant strategy for C-C bond formations – a minireview in Angewandte about catalytic carbonyl addition through transfer hydrogenation, written by Krische, can be found here (but subscribers only, I‘m afraid).

And that’s not to mention typically mesmerising talks from the likes of George Whitesides and Jean-Marie Lehn (who had a slight disagreement regarding a well-used model of molecular recognition – but more on that tomorrow).

I could go on – but for now, I’ll sign off with an ‘au revoir’.

Andy

Andrew Mitchinson (Senior Editor, Nature)

The ACS meeting is over, so I guess it’s time for me to climb aboard the love train and head for home. Oh, alright then, it’ll be a cramped flight to the UK, I was just trying to squeeze in a reference to the Philly sound before I left.

But before I go, here are a few bits and pieces from the meeting that made me think, smile, or both. A lot of them seem to involve Barry Sharpless.

Some quotes:

“A man in California just won the Nobel prize for mixing paint and wine.” – Headline in a Los Angeles newspaper following Barry Sharpless’s Nobel win.

“This lovely picture of Edinburgh is one that I took recently – from the internet.” – Dave Leigh

“You say this was done with a burette? I could do better with a graduated cylinder.” – Comment from William Crowell on a young John Roberts’ titration technique.

“Enzymes are swirly things, they’re spaghetti monsters.” – Barry Sharpless. Surely not a reference to the cult of the spaghetti monster?

Things I learnt at the meeting:

Some chemistry sets 77 years ago included recipes for gunpowder.

‘Detartrated’ is the longest single-word palindrome in the English language, according to Barry Sharpless. (To detartrate means to remove the tartrate from wine.)

The spell-check program on my laptop corrects ‘aldehydes’ to ‘baldheads’.

Other things that made me smile:

Barry Sharpless’s impression of an olefin.

That’s all for now, I’m heading for home sweet home.

Andy

Andrew Mitchinson (Senior Editor, Nature)

I’m going to stick my neck out a bit here, and discuss some chemical biology, even though I wouldn’t claim to be much of a biology expert. Apologies if some of the details are a bit ropy.

This morning, Linda Hsieh-Wilson gave an inspiring talk on her work unravelling the role of the polysaccharide chondroitin sulfate (CS) in modulating neuron growth. Naturally occurring CS is a mixture of compounds, each containing a different pattern of sulfate groups. This makes it difficult to tease out the effects of particular sulfation patterns, but Hsieh-Wilson’s group have made several tetrasaccharides as models of CS, each with one of the different characteristic arrangements of sulfates found in the parent molecule.

They find that only one of these tetrasaccharides (called CS-E) promotes neuron growth in their in vitro studies. Using CS-E as a molecular probe, they’ve now started to unravel the likely biological mechanism of action. It seems that CS-E forms a ternary complex with brain-derived neurotrophic factor and the receptor TrkB. Blocking formation of this complex prevents CS-E-mediated neurite growth.

But CS is a double-edged sword – it can also prevent neuron regeneration after injury. Hsieh-Wilson is now using her compounds to unpick the reasons for this. Her tetrasaccharides weren’t effective substitutes for CS in in vitro models of neuron regeneration, so her team came up with a method to prepare CS-E polymers (containing 25-80 sugar units). Sure enough, these polymers inhibit neuron regeneration, showing that the CS-E sulfation pattern is most likely responsible for the biological effect. Furthermore, an antibody that blocks CS-E activity was able to counteract the inhibition, thus encouraging neuron repair.

Exciting stuff, especially as there is currently no way to stimulate regeneration of damaged neurons. Of course, this is a long way off providing anything that would be therapeutically useful, but just being able to unpick the biological mechanisms that prevent neuron regeneration strikes me as being incredibly useful. And it’s a perfect example of how chemistry can provide tools that answer biological questions.

Andy

Andrew Mitchinson (Senior Editor, Nature)

I’ve been attending so many interesting sessions that it’s been difficult to find time to blog, but I’m going to redress the balance now. First off, I just wanted to mention a terrific talk yesterday from John Bercaw, which gave an update on his work on the mechanism of the Shilov reaction. If you’re not familiar with this reaction, it was one of the seminal discoveries that underpins modern C-H activation chemistry. Unfortunately, it’s stoichiometric, but Bercaw is hoping to make a catalytic version that will provide a practical method of converting alkanes into alcohols. That goal is still some way off, but he’s found some promising water-compatible catalysts (water compatibility will be essential) that look like a good step in the right direction. I was particularly impressed by his obviously meticulous approach to research – if anyone can crack this problem, then he can.

Then yesterday afternoon, I attended a star-studded symposium that celebrated the 100th birthday of the organic chemistry division of the ACS. With speakers such as David MacMillan, Ken Houk, Larry Overman, K. C. Nicolaou and Barry Sharpless, this was the must-see event of the symposium, and the massive ballroom venue was packed. Befitting the anniversary theme, each speaker gave their perspective of historical advances from their fields of interest.

So how do you pick out a highlight from such an illustrious line-up? With difficulty, but my favourite speaker was John Roberts, the emeritus professor from Caltech. At 90 years old, he’s certainly the most senior speaker that I’ve seen at a conference. I have a fondness for the history of chemistry, so I lapped up Roberts’ stories of his early career, and his reminiscences about the leading figures of the time. For example, R. B. Woodward was described as having three trademarks – he always carried a cigarette, always used a yellow pencil and invariably dressed entirely in blue. Other snippets included the details of Roberts’ work during the Second World War, when he was co-opted onto a project to find a way of extracting liquid oxygen from air at low pressure (because airplanes at the time carried oxygen tanks, which made them rather vulnerable to fires).

Looking back at his project work as a student, Roberts commented that he was lucky in being able to work on several completely different areas. Nowadays, he commented, graduate students specialize early on, and so they miss out on the benefits of a diverse practical training. The solution, he says, is to provide opportunities for undergraduates instead. In this respect, he feels that summer-school research opportunities for undergraduates are essential. Do any of you think that grad students are forced into specializing too soon?

Andy

Andrew Mitchinson (Senior Editor, Nature)

As is traditional for any editor from a Nature journal attending an ACS meeting, let me begin by telling you my own personal trauma in getting here – my plane didn’t have any water in the restrooms for washing your hands. Instead, the airline company improvised by putting out bottles of drinking water for us to use. But I’ll swear that, by the end of the journey, they were using sparkling water in some of the restrooms. Presumably if they’d got really stuck in first class, they’d have started using the champagne.

With that off my chest, let’s talk supramolecular chemistry and molecular motors. I attended a session this morning that showcased some of the younger movers and shakers from organic chemistry, and I especially enjoyed Adam Urbach’s talk, about designing supramolecular binding systems based on cucurbiturils (the name always makes me think of cucumbers, but that‘s probably a problem unique to me). Some cucurbiturils can trap two ‘guest’ compounds simultaneously, and so can be used to hold together appropriately designed molecular units attached on separate peptide chains. This makes it easy to set up two or three binding sites on one chain, which accept the same number of appropriately spaced binding units arranged on another chain. Such systems have previously been difficult to make. Rather neat, I thought.

In the same session, Jonathan Nitschke talked about systems in which a selection of amines, aldehydes and metals react to form a dynamic combinatorial mixture of self-assembling complexes, which eventually reach an equilibrium in which just a couple of products have formed. Nitschke has now reached the point where, for one of his systems at least, he can devise an algorithm that explains the outcome of the equilibrium. Impressive stuff, and I look forward to seeing where this line of research will go next.

But an oscar for cinematography must go to Ben Feringa, who in an afternoon session showed some mind-blowing footage of a dynamic surface rippling with waves, the result of chemical changes in the molecules that make up the surface. David Leigh competed with his movies of droplets of liquid oozing their way up an incline, in response to light-induced changes in the properties of the underlying surface. Amazing. And all the result of rotaxane chemistry.

Day one is over (so fast!) – here’s looking forward to tomorrow.

Andy

Andrew Mitchinson (Senior Editor, Nature)